Mass spectrometer system having synchronously programmable sensitivity

ABSTRACT

A mass spectrometer system for mass fragmentography and method for the same, including a mass spectrometer having a cyclically programmed mass filter for sampling multiple ion mass fragments, and means for programming the mass spectrometer sensitivity in synchronism with the programmed mass filter so that the mass spectrometer sensitivity corresponds with the amplitude of the ion mass fragments sampled.

United States Patent [191 7/1974 Mosharrafa 250/292 X Fies, Jr. 5] Nov. 18, 1975 MASS SPECTROMETER SYSTEM HAVING SYNCHRONOUSLY PROGRAMMABLE Primary Examiner-Davis L. Willis SENSITI Attorney, Agent, or Firm-Flehr, Hohbach, Test, [75] Inventor: William J. Fies, Jr., Portola Valley, Albrmon & Herbert Calif.

[73] Assignee: gliliiifigan Corporation, Sunnyvale, I57] ABSTRACT [22] Filed: Feb. 28, 1974 A mass spectrometer system for mass fragmentography and method for the same, including a mass spec- [211 Appl' 446775 trometer having a cyclically programmed mass filter for sampling multiple ion mass fragments, and means [52] US. Cl 250/282; 250/290 for programming the mass spectrometer sensitivity in [51] Int. Cl. B01D 59/44 synchronism with the programmed mass filter so that [58] Field of Search 250/28 1, 282, 283, 288, the mass spectrometer sensitivity corresponds with the 250/290, 292 amplitude of the ion mass fragments sampled.

[56] References Cited 8 Claims, 2 Drawing Figures UNITED STATES PATENTS .23A DETECTOR) r24 22 t OUTPUT 7 XY I F. I unn- PROGRAMABLE MASS SET I l RF/DC I L VOLTAGE SENSITIVITY l GENERATOR I GENERATOR, 25 SIGNAL PRDG l i 2s 7 1 l I MSVG m I Q N I I RANGE we 21 Rule: m'rs- I SET GRA SET .TOR

3 23 O O I ,nAss MS I ser HOLD 29 ss'r HOLD l CLOCK I I MASS SET l l I CLOCK I OUTPUT v l \IZ PROMIM 1 MULTl-CHANNEL STRIP CHART I RECORDER US. Patent Nov. 18, 1975 Sheet 1 of 2 DE TECTOR I ELECTRON SOURCE 22 OUTPUT 7 x Y l T 1 UNIT PROGRAMABLE I MASS SET L r RF/DC VOLTAGE SENSITIVITY GENERATOR l GENERATOR 25 SIGNAL I 25 A 7 l PRDG l Msv 7 ml C H N I I 32 R'ANeE ME 21 RANGE iNTE- SET eRAToR SET GRATOR I 3| 2e 0 o 0 I /MASS SAMPLE MASS SAMPLE l SET amouf' SET aHoLD I l CLOCK A MASS SET f I 1 lcLocK l 4 OUTPUT L l -l2 PROMIM MULTl-CHANNEL STRIP CHART RECORDER FlGxl CHANNEL 2 I US. Patent Nov. 18, 1975 Sheet 2 of2 3,920,986

CHANNEL I cI-IANNEI. 2 I TIME FRAME (TFI) TIME FRAME (TF 2) n3 I SAMPLE p21 I SAMPLE I m me p l I ti l I II I I I n2 T 2 g I I II I II I SHIFT IN I I II :l I I I II I I I I IL I II l I II I II I I I II I II I A I L I I I II I I I II I II I E] I II I III 'Q L E 'L EHK L I I I I I I I I II I II I 5 l I I H I CLEAIR I} I I I l L IEB1 I B I '1 I I I I III II I II I ME 3 5 H I II I II I III SAML E I-1Q L D II I II I I I II I Ii 2 I II I CHANEEk S|flF T OUT/ I I II I CHANNEL 2 SHIFT IN I I I I l I l L I I I I I II I I III A 1' I I I I I I| I I II Q -BQEEB L-A D II I MASS SPECTROMETER SYSTEM HAVING SYNCI'IRONOUSLY PROGRAMMABLE SENSITIVITY BACKGROUND OF THE INVENTION This invention relates generally to a mass spectrometer system for mass fragmentography including a programmable mass filter and more particularly a system which has synchronously programmable sensitivity.

It is well known in mass spectrometer, mass fragmentography systems that a chemical sample may be bombarded with electrons or otherwise ionized, and the ions may be accelerated through an electrically programmable mass filter, such as an electrostatic quadrupole filter. Only those ions having a mass to charge ratio, m/e, corresponding to the voltages impressed on, and the electrostatic field produced by, the quadrupole filter rods are collected at a detector, such as an electron multiplier. The output from the electron multiplier is an electric current that is proportional to the time rate of arrival of ions and thus is a measure of the amount of the sample having a particular m/e ratio, that is present in the ion source. 'Of course, mass alone is not particularly helpful but the ionization of a sample does produce useful particular mass fragmentation patterns which are characteristic of a particular material or compound.

Although the entire mass spectrum may be recorded and the sample visually identified, it is usually sufficient to record one to five characteristic mass to charge ratios or mass fragments and thereby with a high degree of probability identify the sample. Having a priori knowledge of one to five characteristic m/e ratios it is convenient with a programmable mass filter to simply search the ionized sample for those identifiable m/e raties and if characteristic peaks or responses are produced then the sample has been identified to a high degree of probability. This technique is particularly useful in identifying a particular material or compound in an impure sample, as only those ions passed by the mass filter are detected, to the exclusion of all other ions of the impure sample.

Moreover, monitoring only selected mass fragments greatly improves the mass spectrometer sensitivity over the sensitivity realized in full scan. The instrument is only receptive to the ions needed for the particular measurement, and thus the number of ions collected and used in the analysis may be increased by a factor of one thousand to one over the desired ions collected in full scan. Therefore measurement accuracy, as is well known, increases by the square root of the quantity of ions collected, or approxixmately a thirty three to one improvement in sensitivity.

In many applications it is necessary to measure one mass peak one thousand times larger than another, or one sample which is very large in comparison with another small sample, necessitating monitoring two masses or some combination of masses where the dynamic range is quite large. With the bandwidths needed for these measurements the spectrometer amplifier connected to the electron multiplier must have a range of without range switching. On the other hand, if the amplifier range could be switched at the appropriate time the dynamic range could be extended to 10 However switching the instrument from one mass peak to another mass peak imposes, in practice, a limit on the dynamic range of the instrument. In cyclical switching of the quadrupole instrument from mass peak to another, a plurality of channels modules are required where each module sample one mass peak. The plural channel modules are conventionally combined with cyclical switching such as a programmable multiple ion monitor, PROMIM, to form an extremely useful adjunct to conventional programmable mass filter spectrometers. The instruments can include any number of channels, with a practicaal number being about eight channels. In reality, this limit is established by that number of channels that an operator can practically manipulate during an instrument run. Briefly, these channels time share, that is, they direct the instrument to a particular mass set voltage of a prior interest. The channel module then samples and integrates the current from the instrument detector for a pre-selected sampling period.

At the end of the sampling period each channel module stores the integrated current function in a sample and hold circuit and supplies the output of that channel to a multipin chart recorder. The sampling time of course can be individually adjusted for each channel, but if four channels are to be monitored the instrument may conventionally speed one fourth of the total measurement scan time at each mass fragment.

With such channel switching the dynamic range for sample measurement, without range switching, is approximately one thousand to one. For example. the range between a ten volt and a 10 millivolt peak is representative. Below the 10 millivolt level the noise of the channel switching circuitry in the multiple ion monitor becomes large compared to the signal peaks, the noise masks the lower level peaks and thus further range switching below the 10 millivolt level becomes unusable. Therefore the system dynamic range has suffered from channel switching noise.

OBJECTS AND SUMMARY OF THE INVENTION It is a general object of the present invention to provide an improved mass spectrometer system for mass fragmentography having synchronously programmable sensitivity levels and a method for carrying out said synchronous programming.

It is another object of the present invention to provide an improved mass spectrometer system for mass fragmentography having an improved dynamic mass peak range.

It is another object of the present invention to provide a method for synchronously programming a mass spectrometer system to provide improved mass fragment peak sensitivity.

The foregoing and other objects of the invention are achieved by a mass spectrometer having a cyclically programmed mass filter for sampling multiple ion mass fragments, and means for programming the mass spectrometer sensitivity in synchronism with the programmed mass filter so that the mass spectrometer sensitivity corresponds with the amplitude of the ion mass fragments sampled.

BRIEF DESCRIPTION OF THE DRAWING FIG. 1 is a symbolic block diagram of a mass spectrometer system having synchronously programmable sensitivity in accord with the invention.

FIG. 2 is a mass spectrometer system timing diagram showing the operation of two of plural sampled channels.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring to FIG. 1, the mass spectrometer. mass fragmentography system is shown including mass spectrometer l1, programmable multiple ion monitor. PROMIM. l2 and multichannel strip chart recorder 13.

More particularly, mass spectrometer 11 includes ion source 14 having sample gas inlet 16 and elelctron source 17 aligned to direct electrons through said ion source 14 to bombard sample gas with electrons creating positive ions within ionization region 18. Plural plates 19 and 20 have apertures which are aligned with and focus the ions within the input of quadrupole mass filter 21. Conventionally. plate 19 has a negative potential of approximately 100V impressed thereon. and plate 20 has a voltage equal to the axis potential of the quadrupole field impressed thereon to introduce ions into filter 21 where the are electrostatically filtered according to their mass to change ratio.

Mass filter 21 is a multi-pole mass filter. such as a conventional quadrupole. having a plurality of substantially parallel. coextensive electrodes spaced symmetrieally about a central axis. A first pair of diametrically opposed electrodes. lying in a first plane, is connected to the X coordinante output of Programmable RF/DC Generator. PRDG. 22. A second pair of diametrically opposed electrodes. in a second plane orthogonal to the first plane, is connected to the Y coordinate output of PRDG 22.

A detector-amplifier 23 is positioned at the output of mass filter 21 to collections passing through the mass filter 21.

A detector 23A may conventionally be an electron multiplier having plural dynodes. Detector 23A. an electron multiplier collects the ions which pass through mass filter 21 and has an output connected to the input of the amp 238. In the preferred embodiment. the detector or electron multiplier is combined with an amplifier having a variable feedback path. such as FET switched feedback resistors. A feedback amplifier is important to maintain a wide bandwidth. sufficient to pass mass peak information at the sampling rate hereafter described and to prevent smearing of one peak over another as a result of a restricted bandwidth by virtue a system-contributed time constant. Gain stability in the amplifier is particularly required for isotope ratio measurements as when measuring the ratio between two mass peaks for analytical purposes. A stable, switched gain amplifier is required in the present system, as opposed to applying a switched bucking voltage to a conventional amplifier and attempting to vary the amount of bucking depending of the mass peaks to be viewed. The obvious problem with bucking is that even is used to buck out a particular background mass peak, there is a degrading contribution of statistical noise, and the dynamic range is reduced to a level such that bucking prior to the switching circuits has no advantage to bucking directly at the recorder.

The design of the amplifier included in detectoramplifier 238 must be such that it takes the signal from the output of the electron multiplier included in detector-amplifier 23 and provides a voltage output proportional to the input current. The range switching required typically may be between 10 and 10- am peres per volt. As will be presently seen. the range is switched or programmed within 2, to as much as 12 milliseconds depending on the particular range selected. Range settling time is provided to allow the amplifier to settler and stabilize particularly on the 10- amperes per volt range.

The output of detector-amplifier 23 is connected to the input of output unit 24. Output 24 is of conventional circuitry for conventional manual operation of the mass spectrometer. The output of output unit 24 is connected to the SIGNAL BUS of PROMIM 12. The SENSITIVITY BUS of PROMIM 12 is connected to the sensitivity input of detector-amplifier 23B.

PROMIM 12 includes plural, mass sample channels 25. Each mass sample channel 25 includes a sensitivity range set circuit 26 having an output connected to the SENSITIVITY BUS of PROMIM 12. The SENSITIV- ITY BUS controls the sensitivity of the detectoramplifier 23 by switching the feedback resistors in amplifier 23A. Alternatively, the SENSITIVITY BUS could control the gain of the electron multiplier detector 23A. For example, the SENSITIVY BUS could control the voltage applied to one or more of the dynodes. Also included in PROMIM are an integrator 27 having an input connected to the SIGNAL BUS of PROMIM 12, a mass set 28 having an output connected to the MASS SET BUS of PROMIM 12 and a sample and hold 29 having an output connected to the OUTPUT BUS of PROMIM 12. Each mass sample channel 25 has a clock input connected to a CLOCK BUS of PROMIM 12 which is connected to clock 31. The MASS SET BUS is connected to the input of MASS SET VOLT- AGE GENERATOR, MSVG, 32 which has an output connected to the input of PRDG 22. The OUTPUT BUS of PROMIM 12 is connected to the input of multichannel strip chart recorder 13.

Turning now to operation, the operator first introduces a sample to the mass spectrometer. Any conventional method either using the spectrometer by itself or in conjunction with a gas chromatagraphy may be used. Briefly the sample way be introduced through a conventional batch inlet, that is, as a heated volume where the material is placed in the instrument, so that the volume is of sufficient temperature that the material reaches a gaseous state, and then the sample gas is allowed to flow through a pinhole leak into the instrument inlet 16. Secondly, the sample may be introduced by a solid injection probe where a minute amount of the material, usually from solution, is placed in a gas capillary, and placed at the tip of a probe which is then pushed through an air lock in the mass spectrometer. Subsequently, when the probe is heated the sample is evaporated into the ion source.

A third and most commonly used system is the combination of a gas chromatagraph with the mass spectrometer system. The sample is introduced into the sample inlet of the gas chromatograph and the processed gas chromatograph effulent is then piped through an interface system directly into the mass spectrometer inlet 16 and thereby into ionization region 18.

The gas chromatography, as is well known, will separate a non-pure sample into components for subsequent processing by the mass spectrometer system. Typically the component peaks from the gas chromatograph last from 1 to 10 or perhaps 15 seconds. However the time is sufficient during each component mass peak to carry out an instrumentation run and obtain a mass spectrogram.

Of course the mass spectrometerfrnass fragmentography system is capable "of separating out mass 'peaks, in many situations without first purifying the sar'nple. In particulary, it maybe'desired to analyze the lidocaine content from a patients blood stream. Furthere, it would be desirable tomeasure the idocaine without having to purify the sample first, which in this case would be very difficult and'timef'consuming.

As in the case of with general sample measurement a blood sample is introduced into the mass spectrometer, mass fragmentography system. Having a priori information as to the characteristic mass peaks lidocaine, the operator has set for example, the first mass sample channel 25 controls to correspond to the first known characteristic peak. Mass set 28, range set 26, integrator 27, and sample and hold 29 are adjusted to correspond to the mass set voltage, sensitivity and integration time for .the corresponding first known peak of lidocaine. In like manner, the remainder of the plural mass sample channels 25 are set, as desired, for other known individual characteristic peaks of lidocaine.

In setting up this system each channel of the programmable multiple ion monitor, PROMIM, may be placed on hold, and a sweep voltage applied to an alternate output device such as an oscilloscope (not shown). The operator can then go through a calibration procedure to locate the desired mass peaks either by using a conventional mass marker system, a background gas, or similar conventional calibration methods. The operator then sets each individual mass samplechannel 25 controls including mass set 28 control, range set 26 control, integrator 27 control, and sample and hold 29 having a priori knowledge of the known individual characteristic mass peaks about to be measured. Sequentially, the operator places each individual mass sample channel 25 on hold and calibrates that channels controls to correspond with the expected mass peak characteristic. Once the set up and calibration is completed, the instrumentation run may begin. Next the operator introduces the sample into the mass spectrometer inlet 16 by any of the alternate methods previously described. When sufficient time has passed for the sample to elute, the mass spectrometer, mass fragmentography system begins to sample the ions formed in ionization region 18 as they are focused by plural plates 19 and 20 enter mass filter 21.

Referring to FIG. 2, a system timing diagram is shown for a system having two mass sample channels 25. Channel 1 has a corresponding Time Frame, TF1, and Channel 2 has a corresponding Time Frame TF2. Of course, additional channels 3-N, if incorporated in the system, would have individual corresponding Time Frames, TF3-TFN. Each of plural channels has an adjustable time frame, the first TF1 initiated by clock 31, which starts the scan cycle by providing a master shift CLOCK OUT pulse, ti-l, which may be approximately 2 microseconds in duration, causing the MASS SET signal to go high actuating the pre-set mass control and providing a mass set voltage on the MASS SET BUS. The MASS SET BUS drives MSVG 32 providing a mass set voltage MSVl to PRDG 22 thereby programming filter 21 to a particular mass peak. The RANGE SET signal goes low, actuates the pre-set range sensitivity control on RANGE SET 26 and feeds a range voltage to the SENSITIVITY BUS to select a particular detector-amplifier 23 feedback resistor and thereby determine system sensitivity. The HOLD OFF fjpiirp ose being to provide time for the amplifier in- "chided in deteetor-amplifier'23 and the other portions of the mass spectrometer to settle and stabilize. The CLOCK OUT signal ti l also clears integrator 27. At

v the end of the tc-l period the t-sample period. ts-l, be-

LII

gins, the HOLD OFF DELA Y signal goes high and integrator 27 begins to integrate the signal from output unit 24. The ts-l period is adjustedfor the sample period desired, such as 10 milliseconds. At the end of the ts-l period the integrated signal from integrator 27 provides an input to sample and hold 29. The output of sample and hole 29 drives the OUTPUT BUS and multichannel strip chart recorder 13. The t-load period tl-l is to permit the integrator 27 to update sample and hold 29 with the recently sampled data, which sample and hold 29 then provides as a continuous output to C hannel 1 of mu-lti-channel strip chart recorder 13. The period t,ll is typically 25 microseconds.

At the end of the tl-l pulse. Channel 1 provides a shift out signal ti-2, such as a 2 microsecond pulse, which then starts the next sequential channel. Channel 2. As can be seen from the timing diagram. the tc-2 period then begins for Channel 2 and may again be typically 2 milliseconds. Next the ts-2 period for Channel 2 begins corresponding to the sample time desired, such as again 10 milliseconds. Of course the ts-2 period may be changed within Time Frame TF2, as desired and consonant with the a priori knowledge as to the mass peak which Channel 2 is to sample. Similarly. at the end of the ts-2 sample period for Channel 2 a tl-2 period begins during which integrator 27 in Channel 2 updates sample and hold 29 which then provides a continuous output to Channel 2 of multi-channel strip chart recorder 13. At the end of the tl-2 period an inhibit signal th is provided indicating a full scan has been accomplished. At the end of the inhibit period th2 typically microseconds, the clock 31 is released. and the clock initiates a master shift CLOCK OUT pulse. ti-l, again typically 2 microseconds, beginning the next cyclical full scan period.

Thus it is apparent from the foregoing that there is provided an improved mass spectrometer system for mass fragmentography having synchronously programmable sensitivity levels and a method for carrying out the synchronous programming. Moreover system sensitivity is programmed in the ion detector-amplifier portion of the system to increase weak signal input to the multiple ion monitor and thus override channel switching noise contributed by the multiple ion monitor. Thus a system and method for approved mass fragment peak sensitivity and mass peak dynamic range in a mass fragmentography system is provided.

I claim:

l. A mass spectrometer system for mass fragmentography comprising:

a mass spectrometer having a cyclically scanned mass filter for sampling multiple ion mass fragments over sample time periods, and

means for separately programming the mass spectrometer sensitivity for each mass filter sample time period independent of other sample time periods so that the mass spectrometer sensitivity corresponds with the amplitude of the ion mass fragments sampled.

2. A system in claim 1 wherein said means for programming includes: v

means for varying the spectrometer ion detectoramplifier to pre-selected sensitivity levels for each of pre-selected sample time periods.

3. A system as in claim 2 wherein means for varying includes:

switching the spectrometer ion detector-amplifier to pre-selected sensitivity levels for each of the preselected time periods.

4. A system as in claim 2 wherein the ion detectoramplifier is an electron multiplier in combination with voltage means for varying the electron multiplier dynode voltages whereby the sensitivity of the electron multiplier is varied.

5. A system as in claim 2 wherein the ion detectoramplifier is an electron multiplier in combination with a variable gain amplifier.

6. A system as in claim 5 wherein the variable gain amplifier is an FET switched feedback amplifier.

7. A mass spectrometer system for mass fragmentog- 8 raphy comprising:

a quadropole mass spectrometer. for scanning preselected ion mass fragments for preselected sample time periods in a pre-determined cyclical pattern. said spectrometer including an electron multiplier detector and a feedback amplifier. said spectrometer being additionally programmed to switch the feedback amplifier to pre-selected gain levels for each of the sample time periods.

8. A method for mass fragmentography in a mass spectrometer system comprising the steps of:

providing a mass spectrometer having a cyclically scanned mass filter for sampling multiple ion mass fragments over sample time periods. and programming the mass spectrometer sensitivity separately for each sample period and in synchronism with the programmed mass filter so that the mass spectrometer sensitivity corresponds with the amplitude of the ion mass fragments sampled. 

1. A mass spectrometer system for mass fragmentography comprising: a mass spectrometer having a cyclically scanned mass filter for sampling multiple ion mass fragments over sample time periods, and means for separately programming the mass spectrometer sensitivity for each mass filter sample time period independent of other sample time periods so that the mass spectrometer sensitivity corresponds with the amplitude of the ion mass fragments sampled.
 2. A system in claim 1 wherein said means for programming includes: means for varying the spectrometer ion detector-amplifier to pre-selected sensitivity levels for each of pre-selected sample time periods.
 3. A system as in claim 2 wherein means for varying includes: switching the spectrometer ion detector-amplifier to pre-selected sensitivity levels for each of the pre-selected time periods.
 4. A system as in claim 2 wherein the ion detector-amplifier is an electron multiplier in combination with voltage means for varying the electron multiplier dynode voltages whereby the sensitivity of the electron multiplier is varied.
 5. A system as in claim 2 wherein the ion detector-amplifier is an electron multiplier in combination with a variable gain amplifier.
 6. A system as in claim 5 wherein the variable gain amplifier is an FET switched feedback amplifier.
 7. A mass spectrometer system for mass fragmentography comprising: a quadropole mass spectrometer for scanning pre-selected ion mass fragments for preselected sample time periods in a pre-determined cyclical pattern, said spectrometer including an electron multiplier detector and a feedback amplifier, said spectrometer being additionally programmed to switch the feedback amplifier to pre-selected gain levels for each of the sample time periods.
 8. A method for mass fragmentography in a mass spectrometer system comprising the steps of: providing a mass spectrometer having a cyclically scanned mass filter for sampling multiple ion mass fragments over sample time periods, and programming the mass spectrometer sensitivity separately for each sample period and in synchronism with the programmed mass filter so that the mass spectrometer sensitivity corresponds with the amplitude of the ion mass fragments sampled. 